Nonsense-mediated decay (NMD). A single gene locus is transcribed into a pre-mRNA containing all exons and introns. The left panel illustrates normal splicing when proteins of the exon junction complex (EJC) are deposited ∼20-24 nucleotides upstream of exon-exon boundaries. EJCs are displaced by the scanning ribosome in the ‘pioneer’ round of translation. The right panel illustrates an RNA with a premature termination codon (PTC), that is a stop codon more than 50-55 nucleotides upstream of the final exon-exon boundary. During the pioneer round of translation, EJCs downstream of PTCs are not displaced, triggering degradation by NMD, an mRNA surveillance system. Cap = 7-Methylguanosine; CHX = cycloheximide, a naturally occurring antibiotic that inhibits translation and therefore inhibits NMD; STOP = termination codon.